ArticleThe Journal of clinical investigation2004
Hepatitis C virus mutation affects proteasomal epitope processing.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 139 citations in OpenAlex.
- Prediction of potential NS3-based T cell epitopes of hepatitis C virus by in-silico and in-vitro approach.Scientific reports · 2026Article
- Hepatitis C virus-associated B-cell non-Hodgkin lymphomas: immune evasion, multistep lymphomagenesis, and candidate biomarkers for risk stratification and disease monitoring.Frontiers in immunology · 2026Review
- Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies.International journal of molecular sciences · 2023Article
- Brain endothelial cells exposure to malaria parasites links type I interferon signalling to antigen presentation, immunoproteasome activation, endothelium disruption, and cellular metabolism.Frontiers in immunology · 2023Article
- Proteasomal Processing Immune Escape Mechanisms in Platinum-Treated Advanced Bladder Cancer.Genes · 2022Article
- Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection.Viruses · 2022Review
- Immune escape pathways from the HBV coreFrontiers in immunology · 2022Article
- CD8Frontiers in immunology · 2022Article
- T-Cell Immunity against the Hepatitis C Virus: A Persistent Research Priority in an Era of Highly Effective Therapy.Cold Spring Harbor perspectives in medicine · 2021Review
- Adaptive Immune Response against Hepatitis C Virus.International journal of molecular sciences · 2020Review
- Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination.PLoS pathogens · 2020Article
- A Novel Epitope Quality-Based Immune Escape Mechanism Reveals Patient's Suitability for Immune Checkpoint Inhibition.Cancer management and research · 2020Article
- Mutations in Hepatitis D Virus Allow It to Escape Detection by CD8Gastroenterology · 2019Article
- Hepatitis C Virus Infection: Host⁻Virus Interaction and Mechanisms of Viral Persistence.Cells · 2019Review
- Review
- Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability.Journal of leukocyte biology · 2016Article
- Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).Scientific reports · 2016Article
- Differential Recognition of Influenza A Viruses by M158-66 Epitope-Specific CD8+ T Cells Is Determined by Extraepitopic Amino Acid Residues.Journal of virology · 2016Article
- Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing.Journal of virology · 2016Article
- The T210M Substitution in the HLA-a*02:01 gp100 Epitope Strongly Affects Overall Proteasomal Cleavage Site Usage and Antigen Processing.The Journal of biological chemistry · 2015Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
The high incidence of hepatitis C virus (HCV) persistence raises the question of how HCV interferes with host immune responses. Studying a single-source HCV outbreak, we identified an HCV mutation that impaired correct carboxyterminal cleavage of an immunodominant HLA-A2-restricted CD8 cell epitope that is frequently recognized by recovered patients. The mutation, a conservative HCV nonstructural protein 3 (NS3) tyrosine to phenylalanine substitution, was absent in 54 clones of the infectious source, but present in 15/21 (71%) HLA-A2-positive and in 11/24 (46%) HLA-A2-negative patients with chronic hepatitis C. In order to analyze whether the mutation affected the processing of the HLA-A2-restricted CD8 cell epitope, mutant and wild-type NS3 polypeptides were digested in vitro with 20S constitutive proteasomes and with immunoproteasomes. The presence of the mutation resulted in impaired carboxyterminal cleavage of the epitope. In order to analyze whether impaired epitope processing affected T cell priming in vivo, HLA-A2-transgenic mice were infected with vaccinia viruses encoding either wild-type or mutant HCV NS3. The mutant induced fewer epitope-specific, IFN-gamma;-producing and fewer tetramer(+) cells than the wild type. These data demonstrate how a conservative mutation in the flanking region of an HCV epitope impairs the induction of epitope-specific CD8(+) T cells and reveal a mechanism that may contribute to viral sequence evolution in infected patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.